Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1138174 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29924495_1.fastq.gz | Fastqsanger.gz | |||
| SRR29924495_2.fastq.gz | Fastqsanger.gz | |||
| SRR29924496_1.fastq.gz | Fastqsanger.gz | |||
| SRR29924496_2.fastq.gz | Fastqsanger.gz | |||
| SRR29924497_1.fastq.gz | Fastqsanger.gz |
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Project description:Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism is unelucidated. Here, we identify a central neuroendocrine circuit that directly controls osteogenesis. Using virus based tracing, weidentify that melanin concentrating hormone (MCH) expressing neuronsin the lateral hypothalamus (LH) are connected to the bone.Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis.Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs). Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling and activating MCHR1 by MCH agonists attenuate osteoporosis in mice. By elucidating a brain-bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation.
2025-08-01 | GSE239973 | GEO
Project description:Understanding the dynamic changes of cells during calvarial bone repair is crucial for identifying novel therapeutic targets to enhance bone regeneration. However, the cellular changes and intercellular communication during calvarial defect repair remain poorly understood. To address this, we performed single-cell RNA sequencing on tissues collected at different time points post-defect. Our analysis revealed a significant enhancement in intercellular communication following defect, particularly among stem cells, endothelial cells, pericytes, and macrophages. Pathways related to neurogenesis were significantly enriched after defect. Furthermore, we found that inhibiting sympathetic nerves promoted calvarial bone repair. Mechanistically, sympathetic nerve inhibition enhanced angiogenesis and osteogenesis by promoting interactions between pericytes and endothelial cells, generating a novel senescenced Arg1+ macrophages, which contributed to bone repair by secreting osteogenesis-related cytokines. Besides, inhibition of sympathetic nerves promotes the generation of Shisa3+ suture cell subpopulation and enhances osteogenic differentiation capacity. Importantly, senolytics abrogated the repair benefits brought about by sympathetic nerve inhibition, underscoring the critical role of senescent macrophages in the repair process.
2025-12-31 | GSE298251 | GEO
Project description:Cranial bone defect is a major clinical challenge that increases the life burden of patients. Tricarboxylic acid (TCA) cycle metabolites have recently drawn considerable attention in the field of bone tissue regeneration due to their bio-safety, low cost, structural stability, and effectiveness. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration via a facile and general approach remains lacking. Moreover, the mechanism underlying the release of TCA cycle metabolites from biomaterials in immune responses and mesenchymal stem cells (MSCs) fate (migration and differentiation) remain unknown. Herein, inspired by the Hofmeister effects, we developed a series of TCA metabolite (in the form of sodium salt)-coordinated biomimetic hydrogels (CGG) with strong mechanical and anti-swelling performances. Importantly, the sodium citrate (Na3Cit)-treated CGG hydrogels (CGG-Cit) with the highest mechanical modulus and strength significantly promoted skull bone regeneration in rats and mice. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, we demonstrated that CGG-Cit promotes Gli1+ MSCs migration via neutrophil-secreted OSM. Our results also indicate that CGG-Cit improved osteogenesis via enhanced H3K9ac modification on osteogenic master genes. Taken together, the immune microenvironments and MSCs fate-regulated biomimetic hydrogels developed herein represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.
2024-02-15 | GSE235943 | GEO
Project description:Cranial bone defect is a major clinical challenge that increases the life burden of patients. Tricarboxylic acid (TCA) cycle metabolites have recently drawn considerable attention in the field of bone tissue regeneration due to their bio-safety, low cost, structural stability, and effectiveness. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration via a facile and general approach remains lacking. Moreover, the mechanism underlying the release of TCA cycle metabolites from biomaterials in immune responses and mesenchymal stem cells (MSCs) fate (migration and differentiation) remain unknown. Herein, inspired by the Hofmeister effects, we developed a series of TCA metabolite (in the form of sodium salt)-coordinated biomimetic hydrogels (CGG) with strong mechanical and anti-swelling performances. Importantly, the sodium citrate (Na3Cit)-treated CGG hydrogels (CGG-Cit) with the highest mechanical modulus and strength significantly promoted skull bone regeneration in rats and mice. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, we demonstrated that CGG-Cit promotes Gli1+ MSCs migration via neutrophil-secreted OSM. Our results also indicate that CGG-Cit improved osteogenesis via enhanced H3K9ac modification on osteogenic master genes. Taken together, the immune microenvironments and MSCs fate-regulated biomimetic hydrogels developed herein represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.
2024-02-15 | GSE236134 | GEO
Project description:Orthodontic tooth movement (OTM) is primarily driven by alveolar bone remodeling, wherein tension-induced osteogenesis plays a central role. Importin7 (IPO7) has been identified as a highly mechanoresponsive nuclear transport receptor (NTR). However, its role in regulating tension-induced osteogenesis during OTM and its underlying mechanism remains elusive. In the present study, cyclic tensile strain and a rat OTM model were used to investigate the role of IPO7. The results revealed that IPO7 was significantly expressed both in vitro and in vivo following exposure to mechanical stretch. Moreover, IPO7 knockdown inhibited tension-induced osteogenesis in BMSCs. Upon mechanical force stimulation, IPO7 translocated from the cytoplasm to the nucleus. Furthermore, immunoprecipitation (IP) coupled with mass spectrometry (MS) was performed and demonstrated that RUNX2 was one of the IPO7-interacting proteins related to osteogenesis. Although RUNX2 has been established to translocate to the nucleus to facilitate osteogenesis, whether it is IPO7 that regulate RUNX2 nuclear input during tension-induced osteogenesis remains to be determined. Then, the interaction between IPO7 and RUNX2 was further validated via co-immunoprecipitation (co-IP) and colocalization assays in BMSCs using immunofluorescence. Taken together, this study demonstrates that IPO7 promotes tension-induced osteogenesis by regulating the nucleoplasmic localization of RUNX2. Thus, targeting IPO7 may represent a prospective therapeutic strategy for enhancing alveolar bone remodeling and the efficacy of orthodontic treatment.
2025-10-06 | PXD061760 | Pride
Project description:Inhibiting Connexin 43 (Cx43) hemichannels in osteocytes led to a significant increase in adipogenesis and a decrease in osteogenesis in bone marrow mesenchymal stromal cells.
2024-12-16 | GSE252059 | GEO
Project description:Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration
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Project description:While cellular energy metabolism regulates tissue regeneration, it remains as a challenge with its limited understanding of activation by engineered scaffolds to regenerate tissue or organ for therapeutic purpose. This study presents a biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [abbreviated as P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), functioning as an endogenous bioenergetic molecule to facilitate bone regeneration and promote cellular anabolism via generations of adenosine triphosphate (ATP) and citrate that enhance the progression of human bone marrow mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our studies demonstrate that 3HB not only significantly enhances in vitro ATP generation to elevate mitochondrial membrane potential (ΔΨm) and capillary-like tube formation, but also increases the content of intermediate metabolite, namely, citrate, in tricarboxylic acid (TCA) cycle, and ultimately promotes the formation of citrate-containing apatite during osteogenesis of hBMSCs. Furthermore, 3HB administration increases the bone mass in rats with ovariectomy (OVX)-induced osteoporosis. Results also show that the P(3HB-co-4HB) scaffold significantly enhances long-term induced bone repair in a rat model with critical-sized calvarial defects, compared to the commercialized available poly-L-lactic acid (PLLA) scaffold. Collectively, these findings uncover a previously undefined role of 3HB in promoting osteogenic differentiation of hBMSCs and highlight that the P(3HB-co-4HB) scaffold functions as a metabolically activated energetic material for bone regeneration.
2023-09-03 | GSE242022 | GEO
Project description:In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. Histology and micro-CT analysis demonstrate that Fgf9 S99N mutation (loss-of-function) significantly inhibited the formation of bone marrow adipose tissue (BMAT) in adult mice and alleviated the ovariectomized (OVX) induced bone loss and BMAT accumulation. In vitro cytodifferentiation assays unveiled that the Fgf9 S99N mutation hindered adipogenesis while promoting osteogenesis in BMSCs. Furthermore, recombinant FGF9 stimulation and Fgf9 overexpression in BMSCs demonstrated that Fgf9 significantly promoted adipocyte formation and inhibited osteogenesis in vitro and in vivo. Cytodifferentiation assays at various stages of BMSC differentiation indicated that FGF9 altered the osteogenic and adipogenic potential of BMSCs, particularly during the early stages of differentiation. Transcriptomic and gene expression analyses demonstrated that FGF9 significantly upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. KEEG analysis revealed and in vitro differentiation assays with specific inhibitors confirmed that FGF9 modulated bone-fat balance by inhibiting osteogenesis via the MAPK/ERK pathway and promoting adipogenesis by activating the PI3K/AKT and Hippo pathways.
2024-07-17 | GSE252394 | GEO
Project description:Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Experiment Overall Design: Gene expression profiles were generated from bone marrow MSC before and 1, 3 and 7 days after stimulation with 10E-7M dexamethasone to study the early molecular processes of osteogenic differentiation. 3 replicates per timepoint.
2009-09-18 | E-GEOD-18043 | biostudies-arrayexpress